Oral disease is a serious public health concern due to its significant impact on overall general health and its chronic nature. In the United States, about 4 out of five people suffer from gum disease, and about a fifth of the population has periodontitis (US NIDCR, 2006). Periodontal disease is an infectious disease caused by oral biofilms that are often resistant to treatment, contributing to the chronic nature that can be associated with oral disease. Specifically, periodontal disease is a known risk factor for diabetes (Mealey, 2006), premature or low birth weight in neonates (Romero et al., 2002), and lung and heart disease (Costerton, et al., 1999; Gibson, et al., 2011). Mechanical oral hygiene methods for plaque removal alone do not sufficiently control biofilm accumulation. Further, poor oral hygiene practices in general contribute to poor disease outcome. Numerous studies support the use of an oral rinse for plaque control in addition to mechanical hygiene methods (i.e., toothbrushing), and have shown various degrees of effectiveness dependent on the active ingredients (Decker et al., 2008; Eick et al., 2011; Giertsen, 2004; Hanning et al., 2012; Malhotra et al., 2011; Menendez et al., 2005; Zheng and Wang, 2011). Poor salivary flow leading to xerostomia (i.e., dry mouth) can also lead to poor oral clearance of plaque and excessive cavities. An oral rinse treatment that facilitates the removal of oral biofilms and is well tolerated by sensitive mucosal tissues with minimal side effects would increase patient compliance and support oral health.
Oral bacteria, such as Streptococcus mutans, produce extracellular glucans that facilitate bacterial adhesion to the surface of the tooth. This initial adhesion supports persistent colonization in a nutrient-rich environment (the oral cavity) and facilitates the development of biofilms, which can make treatment more difficult because biofilms are more resistant to antimicrobial agents, biocides, and the host immune response (Loesche, et al., 1986). Biofilms in the mouth are called plaque. Calculus or tartar is a form of hardened dental plaque that is caused by the continual accumulation of minerals from saliva on plaque on the teeth. Oral rinse treatments targeted to remove biofilms may have a greater overall positive impact on the maintenance of good oral hygiene to prevent periodontal disease and associated general health concerns (Costerton, 1999; Ramsey and Whiteley, 2009). Additionally, disagreeable side effects of some products currently in use are: tooth, tongue and restoration discoloration, burning sensation, irritation of mucosal tissue, disturbance of taste, and potentially increased supra-gingival calculus build-up (Charles, et al., 2004; Eley, 1999; Ernst, et al., 2005; Mandel, 1988; Mandel, 1994; Santos, 2003). These undesirable side effects significantly impact patient compliance that may limit the effectiveness of treatment. There remains a need for a safe, well tolerated, and practical aid to reduce the formation of and to remove oral biofilms.
Oral formulations, or mouthwashes or mouth rinses, are often recommended and routinely used by consumers as part of their oral care hygiene regimens. The benefits include control of plaque and calculus formation, removal and prevention of stains, tooth whitening, breath freshening, and overall improvements in mouth feel, impression and aesthetics. Therapeutic benefits include caries prevention through the use of fluoride salts and gingivitis prevention by the use of antimicrobial agents. Other therapeutic benefits of oral rinses include prevention or treatment of infection. Poly (acetyl, arginyl) glucosamine (PAAG) is a novel polycationic biopolymer with unique properties to facilitate the removal of oral biofilms while limiting imbalance of the oral flora and damage to oral mucosa (by current therapies having known cytotoxic ingredients (Baker et al., 2007)). The mechanism of action of PAAG is thought to be similar to other polycationic polymers that work by binding the bacterial cell membrane and disrupting biofilm extracellular polymeric substance (EPS) matrix through interactions with negatively charged phospholipids and structural polymers. PAAG has been shown to rapidly aggregate bacteria. Further, the positive charge allows the PAAG oral rinse formulation to be soluble and active at pH 7, reducing possible irritation and enamel etching, which may be caused by other acidic oral products.
The present invention relates to an oral formulation of PAAG that, alone or in combination with a non-fermentable sugar (e.g., a plurality of non-fermentable sugars), and other inactive ingredients, improves efficacy in prevention of plaque formation and improved plaque and bacterial removal. Surprisingly, when used in combination with a non-fermentable sugar, lower concentrations of PAAG may be used (relative to a formulation without a non-fermentable sugar) to reach a therapeutically effective amount. Therapeutic formulations (e.g., of PAAG, alone or in combination with a non-fermentable sugar (e.g., a plurality of non-fermentable sugars)) may prevent and treat gingivitis, periodontitis, xerostomia and other oral diseases, including infection and from complications after tooth extraction or oral surgery. In addition, the formulation may be effective for the treatment and prophylaxis of mucositis and stomatitis of the oral cavity.